Does prophylactic decompression of distal nerves following nerve repair improve functional recovery? A systematic review.

BACKGROUND: Peripheral nerve injuries are burdensome on healthcare systems, individuals and society as a whole. The current standard of treatment for neurotmesis is primary neurorrhaphy or nerve grafting. However, several patients do not recover their full function. There has been a suggestion that primary distal neurolysis at common entrapment sites maximises surgical outcomes; however, no guidelines exist on this practice. This scoping review aims to ascertain the existing evidence on prophylactic distal decompression of peripheral nerves following repair. METHODS: A literature search was performed using Ovid Medline, PubMed, Embase and Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews for studies published in the past 50 years. Studies were screened using a selection criteria and study quality was assessed using standardised tools. Furthermore, thematic content analysis was performed. RESULTS: Six studies were eligible for inclusion after screening; all studies were retrospective and at most level 3 evidence. No studies were designed specifically to assess the efficacy of distal neurolysis following proximal repair, thus no comparative data with control cohorts are available. All studies that recommended distal decompression of proximally repaired nerves based their conclusions on cases observed by the authors in practice or from theories on nerve regeneration. CONCLUSIONS: This systematic review suggests that the evidence on the role of immediate distal neurolysis in primary neurorrhaphy is inadequate. Recommendations are limited by the lack of large-scale and generalisable data. Further research is needed with definitive objective outcomes and patient-related outcome measures.

Perspectives and challenges in lip rejuvenation: a systematic review.

OBJECTIVE: There is an abundance of information on facelifts, blepharoplasties, rhinoplasty, and other cosmetic surgical procedures for the upper third of the face, but little is known about perioral lip rejuvenation. The aim of this article is to examine the existing literature on lip rejuvenation and perioral procedures related to lip rejuvenation. Additionally, this article aims to highlight the importance of addressing perioral areas alongside lip rejuvenation procedures, rather than solely focusing on lip rejuvenation. We also discussed the extensive procedures and materials used for lip rejuvenation, such as hyaluronic acid, botulinum toxin A, abobotulinum, onabotulinum, incobotulinum, prabobotulinum, fat grafts, silicone fillers, human collagen, collagen stimulating procedures such as derma pens and derma rolls, radiation frequency, stem cells, and plasma therapy, as well as the underlying factors that contribute to varying success rates. MATERIALS AND METHODS: A thorough literature search was done using PubMed, Cochrane, Ebsco search, Google Scholar, Scopus, and Web of Science for the articles pertaining to facial and lip cosmetic surgeries 1995-2020. Keywords for the search included anatomy of the face, facial aging, perioral areas, lip rejuvenation, botox, grafts, facelift, plastic surgery, stem cell therapy, plasma treatment, and cosmetic surgery. RESULTS: 37 articles met the study criteria. 14 out of 37 studies included procedures for lip and perioral region rejuvenation. The remaining 23 studies either involved lip procedures alone or lip procedures in conjunction with facial cosmetic procedures. Lip rejuvenation with perioral enhancement with hyaluronic acid gel demonstrated a 94.3% improvement on the lip fullness scale (LFS) one month after re-treatment. The amalgamation of lip and perioral region rejuvenation produces a synergistic effect. Whereas, sole lip rejuvenation procedures showed short-term results with less patient satisfaction, calling for secondary lip rejuvenation procedures. It was also observed that hyaluronic acid was the most commonly used agent for lip rejuvenation procedures with minimal or no side effects. CONCLUSIONS: In conjunction with perioral rejuvenation, lip rejuvenation procedures produce more aesthetically appealing results. However, any cosmetic surgical or non-surgical procedure is limited by the nature and composition of the products used. The use of FDA-approved products for rejuvenation is strongly advised to avoid undesirable side effects. Further extensive research is required on the long-term outcomes and adverse effects of stem cell transplants, such as tumor development.

Theoretical studies of phosphorene as a drug delivery nanocarrier for fluorouracil.

The interactions between phosphorene nanosheets (PNSs) and 5-fluorouracil (FLU) were explored using the density functional theory (DFT) method and molecular dynamics (MD) simulations. DFT calculations were performed utilizing M06-2X functional and the 6-31G(d,p) basis set in both gas and solvent phases. Results showed that the FLU molecule is adsorbed horizontally on the PNS surface with an adsorption energy (Eads) of -18.64 kcal mol-1. The energy gap (Eg) between the highest occupied and lowest unoccupied molecular orbitals (HOMO and LUMO, respectively) of PNS remains constant after the adsorption process. The adsorption behavior of PNS is not affected by carbon and nitrogen doping. The dynamical behavior of PNS-FLU was studied at T = 298, 310, and 326 K reminiscent of room temperature, body temperature, and temperature of the tumor after exposure to 808 nm laser radiation, respectively. The D value decreases significantly after the equilibration of all systems so that the equilibrated value of D is about 1.1 × 10-6, 4.0 × 10-8, and 5.0 × 10-9 cm2 s-1 at T = 298, 310, and 326 K, respectively. About 60 FLU molecules can be adsorbed on both sides of each PNS, indicating its high loading capacity. PMF calculations demonstrated that the release of FLU from PNS is not spontaneous, which is favorable from a sustained drug delivery point of view.

Exploration of phosphorene as doxorubicin nanocarrier: An atomistic view from DFT calculations and MD simulations.

Potential capability of phosphorene nanosheet (PNS) as doxorubicin (DOX) nanocarrier was investigated using density functional theory (DFT) method and molecular dynamics (MD) simulations. Both DFT calculations and MD simulations revealed that the DOX molecule is adsorbed horizontally onto the PNS surface with the nearest interaction distance of 2.5 Å. The binding energy of DOX is predicted to be about - 49.5 kcal.mol-1, based on the DFT calculations. After DOX adsorption, the Eg value of PNS remains almost constant in both gas and solvent phases. The dynamical behavior of PNS-DOX was studied at T = 298, 310, and 326 K that reminiscent of room temperature, body temperature, and temperature of tumor after exposure to 808 nm laser radiation, respectively. The diffusion coefficient values of DOX molecule are proportional to temperature. We found that PNS can hold a high amount of DOX on both sides of its surface (66% in weight). MD simulations showed that the dynamical behavior of simulated systems are not affected by pH variances.

[Mazabraud syndrome]. / Síndrome de Mazabraud.

Mazabraud syndrome was first described in 1926 by Henschen, consisting of the association between bone fibrodysplasia and one or more intramuscular myxomas. The study paper conducted by Mazabraud et al. in 1967, described an association between the two pathologies. Later literature referred to this relationship with the eponym described above. In this report, we present the case of a 43-year-old female patient with a known diagnosis of bone fibrodysplasia and subsequent development of a right antecubital fossa mass, which was histologically confirmed as intramuscular myxoma. After the removal of the tumor, the literature was reviewed to find a possible relationship between myxomas and fibrous bone dysplasia, finding positive the association, referred to in the documents reviewed as Mazabraud syndrome.

El síndrome de Mazabraud fue descrito inicialmente en 1926 por Henschen, consiste en la asociación entre fibrodisplasia ósea y uno o más mixomas intramusculares. El documento de estudio realizado por Mazabraud y colaboradores en 1967 describió una asociación entre las dos patologías. Literatura posterior se refirió a esta relación con el epónimo antes descrito. En este reporte, presentamos el caso de una mujer de 43 años, con diagnóstico conocido de fibrodisplasia ósea y posterior desarrollo de una masa en fosa antecubital derecha, la cual fue confirmada histológicamente como mixoma intramuscular. Después de la extracción de la tumoración, se revisó la literatura para encontrar una posible relación entre mixomas y displasia ósea fibrosa, encontrando positiva la asociación, denominada en los documentos revisados como síndrome de Mazabraud.

PAMAM and polyester dendrimers as favipiravir nanocarriers: a comparative study using DFT method.

The electronic sensitivity and reactivity of polyamidoamine (PAMAM) and polyester dendrimers toward favipiravir (T705) were inspected using density functional theory method. The T705 drug is adsorbed on the surface of PAMAM and polyester dendrimers with the binding energy of -27.26 and -26.80 kcal mol-1, respectively, in the solvent phase. The energy gap of PAMAM and polyester dendrimers reduced by about 32% and 27%, indicating that the electrical conductance of carriers become 8.16 × 1023 and 4.41 × 1022 times higher, upon T705 adsorption. The work function (Φ) value of PAMAM and polyester is changed about 1.53 and 0.71 eV, respectively. Thus, PAMAM dendrimer is about 2.5 times stronger Φ-type sensor than polyester dendrimer. The recovery time for T705 desorption from the PAMAM and polyester surface is predicted to be 9.2 × 103 and 4.2 × 103 s, respectively, at physiological environment.

CNT-based nanocarrier loaded with pyrimethamine for adipose mesenchymal stem cells differentiation and cancer treatment: The computational and experimental methods.

Pyrimethamine is an effective drug in the cancer cell treatment and is a dihydrofolate reductase inhibitor. In this work, the amount of drug loading up on CNT and its cytotoxicity effect upon MCF-7 cell lines was surveyed. The novel applications of some drugs and nanocarriers can induce the differentiation of adipose mesenchymal cells into nerve cells. Hence carbon nanotube-pyrimethamine was used to differentiate mesenchymal stem cells into the neural category, for the first time. The results of NSE and NFM gene expression level were evaluated using the real-time PCR. A detailed study on the interaction between pyrimethamine anticancer drug and (6, 0) zigzag single-walled carbon nanotube was performed by DFT/B3LYP and DFT/M06-2X with 6-31G* basis set calculations in gas phase and in solvent using the PCM. Different configurations of the adsorbed pyrimethamine onto the CNT surface were studied. Based on the results, the process of pyrimethamine adsorption on diff ;erent sites on the outer wall of the nanotube was exothermic and configurations were stable. The adsorption energy values indicated that the pyrimethamine molecule could be physically adsorbed on the external surface of the SWCNT. The QTAIM was used for characterizing the nature of the interactions between the pyrimethamine and the selected nanocarrier.

Tracing chirality, diameter dependence, and temperature-controlling of single-walled carbon nanotube non-covalent functionalization by biologically compatible peptide: insights from molecular dynamics simulations.

Biological applications of single-walled carbon nanotubes (SWCNTs), including drug delivery, require their functionalization with various functional groups such as peptides. Recently, a biologically compatible peptide (named PW3 with the sequence of NH2-Trp-Val-Trp-Val-Trp-Val-Lys-Lys-COOH) has been introduced as a good candidate for modification of carbon nanotubes due to its high affinity toward the exterior surface of these nano-carriers. In order to optimize the process of SWCNT peptide functionalization, the effects of chirality and diameter of SWCNTs as well as the temperature on PW3 adsorption were systematically investigated using molecular dynamics (MD) simulation. It was found that modification of chiral/zigzag SWCNT by PW3 peptide was more suitable compared with the armchair system due to the strong peptide-nanotube interactions and more water solubility at 310 K which can be well explained by microscopic structural investigations. Regarding the enhanced peptide-chiral nanotube interactions at the low temperature of 277 K, chiral nanotubes can be effective structures for SWCNT functionalization process at reduced temperatures. Our analysis indicated that disrupted PW3 and SWCNT hydration patterns and fewer internal interactions within the peptide could be responsible for the stronger peptide modification of SWCNT at higher temperatures. Additionally, "PW3/SWCNT" systems containing larger tube diameters formed more stable complexes owing to their effective surface area increment.

Density functional theory evaluation of pristine and BN-doped biphenylene nanosheets to detect HCN.

Hydrogen cyanide (HCN) adsorption on pristine and B-N doped biphenylene nanosheets was investigated by means of density functional theory calculations. According to biphenylene geometry, all distinct possible B-N substitutions were designed. Adsorption energy and electronic structure at the level of M062X/6-31 g (d,p) theory were computed for all possible geometries. Our results reveal that pristine biphenylene nanosheet is not a suitable candidate for HCN detection. Also, for B-N doping, the sensitivity of the nanosheet depends on the B-N doped configuration. One of these derivative structures shows higher sensitivity to HCN adsorption due to the greater change in electronic properties. Moreover, atoms in molecules and natural bond orbital analysis were performed to obtain more in-depth knowledge about the adsorption mechanism. The range of energy for interaction between HCN and the nanosheets belongs to physical adsorption.

Influence of dendrimer surface chemistry and pH on the binding and release pattern of chalcone studied by molecular dynamics simulations.

Poly(amidoamine) (PAMAM) dendrimers are promising nanocarriers that can enhance the solubility of hydrophobic drugs. The surface chemistry of dendrimers is of great relevance as end groups of these nanocarriers can be easily modified to improve the bioavailability and sustained release of the cargo. Therefore, a molecular-level understanding of the host-guest interactions that can give both qualitative and quantitative information is particularly desirable. In this work, fully atomistic molecular dynamics simulations were used to study the association of a bioactive natural product, ie, chalcone, with amine-, acetyl-, and carboxyl-terminated PAMAM dendrimers at physiological and acidic pH environments. Amine- and carboxyl-terminated PAMAM dendrimers have an open microstructure at low pH that is not able to hold the ligand tightly, resulting in an unfavorable encapsulation of the chalcone molecule. In the case of acetyl-terminated dendrimer, chalcone molecule diffuses out of the dendritic cavities a few times during the simulation time and prefers to locate close to the surface of dendrimer. Average center of mass distance values at neutral pH showed that the chalcone molecule bounds firmly in the internal pockets of amine-, acetyl-, and carboxyl-terminated dendrimers and forms stable complexes with these nanovectors. The potential of mean force calculations showed that the release of the ligand from the dendrimers occurs at a controlled rate in the body.

Bare surface of gold nanoparticle induces inflammation through unfolding of plasma fibrinogen.

The surface of nanoparticles (NPs) get coated by a wide range of biomolecules, upon exposure to biological fluids. It is now being increasingly accepted that NPs with particular physiochemical properties have a capacity to induce conformational changes to proteins and therefore influence their biological fates, we hypothesized that the gold NP's metal surface may also be involved in the observed Fg unfolding and inflammatory response. To mechanistically test this hypothesis, we probed the interaction of Fg with gold surfaces using molecular dynamic simulation (MD) and revealed that the gold surface has a capacity to induce Fg conformational changes in favor of inflammation response. As the integrity of coatings at the surface of ultra-small gold NPs are not thorough, we also hypothesized that the ultra-small gold NPs have a capacity to induce unfolding of Fg regardless of the composition and surface charge of their coatings. Using different surface coatings at the surface of ultra-small gold NPs, we validated this hypothesis. Our findings suggest that gold NPs may cause unforeseen inflammatory effects, as their surface coatings may be degraded by physiological activity.

Atomistic computer simulations on multi-loaded PAMAM dendrimers: a comparison of amine- and hydroxyl-terminated dendrimers.

Poly(amidoamine) (PAMAM) dendrimers have been extensively studied as delivery vectors in biomedical applications. A limited number of molecular dynamics (MD) simulation studies have investigated the effect of surface chemistry on therapeutic molecules loading, with the aim of providing insights for biocompatibility improvement and increase in drug loading capacity of PAMAM dendrimers. In this work, fully atomistic MD simulations were employed to study the association of 5-Fluorouracil (5-FU) with amine (NH2)- and hydroxyl (OH)-terminated PAMAM dendrimers of generations 3 and 4 (G3 and G4). MD results show a 1:12, 1:1, 1:27, and 1:4 stoichiometry, respectively, for G3NH2-FU, G3OH-FU, G4NH2-FU, and G4OH-FU complexes, which is in good agreement with the isothermal titration calorimetry results. The results obtained showed that NH2-terminated dendrimers assume segmented open structures with large cavities and more drug molecules can encapsulate inside the dendritic cavities of amine terminated dendrimers. However, OH-terminated have a densely packed structure and therefore, 5-FU drug molecules are more stable to locate close to the surface of the dendrimers. Intermolecular hydrogen bonding analysis showed that 5-FU drug molecules have more tendency to form hydrogen bonds with terminal monomers of OH-terminated dendrimers, while in NH2-terminated these occur both in the inner region and the surface. Furthermore, MM-PBSA analysis revealed that van der Waals and electrostatic energies are both important to stabilize the complexes. We found that drug molecules are distributed uniformly inside the amine and hydroxyl terminated dendrimers and therefore, both dendrimers are promising candidates as drug delivery systems for 5-FU drug molecules.

DFT, QTAIM, and NBO studies on the trimeric interactions in the protrusion domain of a piscine betanodavirus.

Crystal structure of the protrusion domain (P-domain) of the grouper nervous necrosis virus (GNNV) shows the presence of three-fold trimeric protrusions with two asymmetrical calcium cations along the non-crystallographic three-fold axis. The trimeric interaction natures of the interacting residues and the calcium cations with the neighboring residues within the trimeric interface have been studied by the quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analyses in the framework of the density-functional theory (DFT) approach. The results revealed that residues Leu259, Val274, Trp280, and Gln322 of subunit A, Arg261, Asp275, Ala277, and Gln322 of subunit B, Leu259, Asp260, Arg261, Ala277, Val278, and Leu324 of subunit C are the main residues involved in the trimeric interactions. Charge-dipole, dipole-dipole, and hydrogen bonding interactions make the significant contributions to these trimeric interactions. Among different interacting residues within trimeric interface, residue pair Arg261 B-Leu259C forms the strongest hydrogen bond inside the interface between subunits B and C. It was also found that calcium cations interact with residues Asp273, Val274, and Asp275 of subunits A, B, and C through charge-charge and charge transfer interactions.

Risk Factors of Voice Disorders and Impact of Vocal Hygiene Awareness Program Among Teachers in Public Schools in Egypt.

OBJECTIVES: Even though many studies have explored the problem of voice disorders among teachers worldwide, this problem is still not adequately studied in Egypt. The following study was conducted to investigate the risk factors of voice disorders among an Egyptian sample of school teachers, to measure the effect of a vocal hygiene awareness program on them, and to investigate their vocal cord lesions. METHODS: One hundred fifty-six teachers working in public schools and 180 administrative workers in the Faculty of Medicine in the same city participated in this study. They completed a self-administered questionnaire investigating voice disorders, and were subjected to a voice awareness program and a clinical examination. RESULTS: Voice-related symptoms and Voice Handicap Index were statistically significantly higher among teachers compared with the control subjects. Work duration and high frequency of classes per week of ≥15 were the most statistically significant indicators influencing a teacher's voice. Three months after application of vocal hygiene awareness program, the teachers who were studied showed a statistically significant increase in their awareness about vocal hygiene tips. CONCLUSIONS: Egyptian teachers working in public schools are dealing with classes that include a great number of students per class. They also have to deal with unprofessional facilities and limited assisting resources. Therefore, they are highly exposed to the risk of voice-related disorders. Increasing awareness about healthy behavior with the voice in their occupations will help in improving their quality of work and in minimizing any permanent impairments and/or disability.

DFT Studies of NH-Cl Hydrogen Bond of Amino Acid Hydrochloride Salts in Ion Channels.

Quantum chemical calculations were made, to study NH-Cl hydrogen bonds of two amino acid hydrochloride salts called alanine and threonine. The Nuclear Magnetic Resonance and Nuclear Quadrupole Resonance parameters for nitrogen and chlorine were calculated via four functionals such as, B3LYP, M062X, M06L, and CAM-B3LYP and by applying the 6-311++G(d,p) basis set. One of the functionals produced more accurate results. Geometry optimization was performed using the M062X/6-31++G(d,p) method, and Natural Bond Orbitals analysis was performed by applying the M062X/6-311++G(d,p) level. This study examined Nuclear Magnetic Resonance and Nuclear Quadrupole Resonance parameters with changes in structure from monomer to pentamer and investigated correlations between Natural Bond Orbitals parameters and Nuclear Magnetic Resonance or Nuclear Quadrupole Resonance parameters. The Natural Bond Orbitals parameters were used to investigate changes in structural parameters along with crystal development.

A theoretical study on the characteristics of the intermolecular interactions in the active site of human androsterone sulphotransferase: DFT calculations of NQR and NMR parameters and QTAIM analysis.

A theoretical study at the level of density functional theory (DFT) was performed to characterize noncovalent intermolecular interactions, especially hydrogen bond interactions, in the active site of enzyme human androsterone sulphotransferase (SULT2A1/ADT). Geometry optimization, interaction energy, (2)H, (14)N, and (17)O electric field gradient (EFG) tensors, (1)H, (13)C, (17)O, and (15)N chemical shielding (CS) tensors, Natural Bonding Orbital (NBO) analysis, and quantum theory of atoms in molecules (QTAIM) analysis of this active site were investigated. It was found that androsterone (ADT) is able to form hydrogen bonds with residues Ser80, Ile82, and His99 of the active site. The interaction energy calculations and NBO analysis revealed that the ADT molecule forms the strongest hydrogen bond with Ser80. Results revealed that ADT interacts with the other residues through electrostatic and Van der Waals interactions. Results showed that these hydrogen bonds influence on the calculated (2)H, (14)N, and (17)O quadrupole coupling constants (QCCs), as well as (1)H, (13)C, (17)O, and (15)N CS tensors. The magnitude of the QCC and CS changes at each nucleus depends directly on its amount of contribution to the hydrogen bond interaction.

Waardenburg syndrome type I: Dental phenotypes and genetic analysis of an extended family.

BACKGROUND: The aim of this study was to describe the pattern of inheritance and the clinical features in a large family with Waardenburg syndrome type I (WS1), detailing the dental abnormalities and screening for PAX3 mutations. MATERIAL AND METHODS: To characterize the pattern of inheritance and clinical features, 29 family members were evaluated by dermatologic, ophthalmologic, otorhinolaryngologic and orofacial examination. Molecular analysis of the PAX3 gene was performed. RESULTS: The pedigree of the family,including the last four generations, was constructed and revealed non-consanguineous marriages. Out of 29 descendants, 16 family members showed features of WS1, with 9 members showing two major criteria indicative of WS1. Five patients showed white forelock and iris hypopigmentation, and four showed dystopia canthorum and iris hypopigmentation. Two patients had hearing loss. Dental abnormalities were identified in three family members, including dental agenesis, conical teeth and taurodontism. Sequencing analysis failed to identify mutations in the PAX3 gene. CONCLUSIONS: These results confirm that WS1 was transmitted in this family in an autosomal dominant pattern with variable expressivity and high penetrance. The presence of dental manifestations, especially tooth agenesis and conical teeth which resulted in considerable aesthetic impact on affected individuals was a major clinical feature. CLINICAL RELEVANCE: This article reveals the presence of well-defined dental changes associated with WS1 and tries to establish a possible association between these two entities showing a new spectrum of WS1.

Interplay between tetrel and triel bonds in RC6H4CN⋯MF3CN⋯BX3 complexes: A combined symmetry-adapted perturbation theory, Møller-Plesset, and quantum theory of atoms-in-molecules study.

Intermolecular ternary complexes composed of: (1) the centrally placed trifluoroacetonitrile or its higher analogs with central carbon exchanged by silicon or germanium (M = C, Si, Ge), (2) the benzonitrile molecule or its para derivatives on one side, and (3) the boron trifluoride of trichloride molecule (X = F, Cl) on the opposite side as well as the corresponding intermolecular tetrel- and triel-bonded binary complexes, were investigated by symmetry-adapted perturbation theory (SAPT) and the supermolecular Møller-Plesset method (MP2) at the complete basis set limit for optimized geometries. A character of interactions was studied by quantum theory of atoms-in-molecules (QTAIM). A comparison of interaction energies and QTAIM bond descriptors for dimers and trimers reveals that tetrel and triel bonds increase in their strength if present together in the trimer. For the triel-bonded complex, this growth leads to a change of the bond character from closed-shell to partly covalent for Si or Ge tetrel atoms, so the resulting bonding scheme corresponds to a preliminary stage of the SN2 reaction. Limitations of the Lewis theory of acids and bases were shown by its failure in predicting the stability order of the triel complexes. The necessity of including interaction energy terms beyond the electrostatic component for an elucidation of the nature of σ- and π-holes was presented by a SAPT energy decomposition and by a study of differences in monomer electrostatic potentials obtained either from isolated monomer densities, or from densities resulting from a perturbation with the effective field of another monomer.

Impact of progesterone and estradiol treatment before the onset of the breeding period on reproductive performance of Bos indicus beef heifers.

The present aimed to develop a hormonal therapy based on the insertion of a progesterone (P4) insert (PI) during 10 d plus an estradiol injection (E2) at PI removal before the onset of breeding of beef heifers. In Exp. 1, the plasma P4 profile of prepubertal heifers showed that the insertion of a PI or 24 d previously used P4 insert (UPI) sustained plasma P4 above 1 ng/mL for at least the first 7 d of the treatment. In Exp. 2 there was no positive effect of additional estradiol benzoate (EB) administered at the insertion of UPI on the proportion of heifers with a corpus luteum (CL/Treated) 30 d after UPI removal [UPI + EB = 85.3%(a) (n = 134); EB + UPI + EB = 80.8%(a) (n = 125)]; however, both were greater (P < 0.0001) than the Control group [60.3%(b) (n = 129)]. In Exp. 3, a positive effect (P=0.01) of UPI treatment and both E2 supplementations [EB and estradiol cypionate (EC); P = 0.10] at the UPI removal was observed on CL/Treated [Control = 42.5%(b) (n = 94); UPI = 58.5%(a) (n= 130); UPI + EB = 64.0%(a) (n = 128); UPI + EC = 67.2%(a) (n = 128)]. However, greater pregnancy per treated heifer (P/Treated) following artificial insemination (AI) upon estrus detection was achieved when EC was applied [Control = 20.2%(b); UPI = 29.2%(ab); UPI + EB = 26.6%(b); UPI + EC = 36.7%(a)]. In Exp. 4, the treatment prior to the timed AI (TAI) tended to improve pregnancy per TAI [P/AI; Control 43.6% (n = 298) vs. UPI+EC 51.9% (n = 342); P = 0.08], but increased P/Treated [26.5% vs. 43.3%; P < 0.001]. Thus, UPI + EC treatment were efficient in increasing the CL/Treated, tended to improve the P/AI and consequently enhanced P/Treated of zebu beef heifers.